VHL and cancer: In 2020, Wang group developed a SHP2 degrader 60 (SHP2-D26, Fig. 17) conjugated with the SHP2 inhibitor SHP099 and VHL ligand.114 The degrader 60 (SHP2-D26) could induce the rapid and efficient degradation of SHP2 protein in KYSE520 cells (DC50 = 6.0 nM) and MV4; 11 cells (DC50 = 2.6 nM), and was capable of reducing SHP2 protein levels by more than 95% in cancer cells.